title: Endothelial colony-forming cell coating of pig islets prevents xenogeneic instant blood-mediated inflammatory reaction.
abstract: Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in islet transplantation. Endothelial colony-forming cells (ECFCs) display unique abilities to promote angiogenesis and repair vascular injury compared to those of endothelial cells (ECs), which inhibits the  allogeneic and xenogeneic IBMIR. We investigated the coating of pig islets with ex vivo-expanded ECFCs as a strategy to overcome xenogeneic IBMIR. Porcine islets were cocultured with human ECFCs in a specially modified culture medium for 2 days to obtain 70-90% coverage. The coating  of pig islets with human ECFCs did not affect the glucose-stimulated insulin secretion capacity or diabetes reversal rate after the transplantation of a marginal islet mass under the kidney capsules of diabetic nude mice compared to that of untreated islets. Uncoated islets, PBS control without  islets, and the ECFC-coated islets were examined with an in vitro tubing loop assay using human blood. After 60 min of incubation in human blood, the ECFC-coated islets showed platelet consumption inhibition and low C3a and TAT assay results compared to those of the uncoated islets. Furthermore,  there was very little macroscopic or microscopic clotting in the human ECFC-coated pig islets. The protective effect was more prominent compared to that of human EC coating of pig islets in our previous study. We investigated the changes in human-specific MCP-1, IL-8, and tissue factor (TF)  levels after the coating of pig islets with human ECFCs or human ECs. The IL-8 levels after coating pig islets with ECFCs were significantly lower than those after coating pig islets with ECs, but there were no significant differences in the MCP-1 or TF levels between the ECFCs and ECs. In  conclusion, the coating of pig islets with ECFCs completely prevented all components of xenogeneic IBMIR. ECFCs may be a better source of protection against xenogeneic IBMIR than are mature ECs.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. jaehyeon@skku.edu
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Bae Jun
authors.initials: BJ
authors.lastname: Oh
authors.forename: Han Na
authors.initials: HN
authors.lastname: Lee
authors.forename: Ho Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Park
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D015926:Complement C3a / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D016209:Interleukin-8 / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010447:Peptide Hydrolases / Q000378:metabolism; D034421:Sus scrofa; D013925:Thromboplastin / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007328:Insulin; D016209:Interleukin-8; C046193:antithrombin III-protease complex; D015926:Complement C3a; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases